Foal Amikacin Final Results 2.25.2019a.xlsx

Six healthy neonatal foals (4 Quarter Horses & 2 Paint horses; 5 colts & 1 filly; mean ± SD weight at 7 days of age at start of study, 59.7 ± 8.0 kg; weight at 24 days of age at end of last protocol 85.2 ± 11.9 kg) completed three amikacin treatment protocols in a randomised cross-over design. Two additional foals did not complete all three protocols. All procedures were approved by and carried out in accordance with the Institutional Animal Care and Use Committee (ACUP# VM-17-20). All foals had adequate transfer of passive immunity as assessed by a blood IgG level of >800 mg/dL (SNAP Foal IgG test)^a at 12-24 hours post-partum. Treatment protocols commenced at 7, 14, and 21 days of age. The three treatment protocols were: 1) administration of 25 mg/kg bwt of amikacin sulphate (Amiglyde-V®)^b IV once daily for three consecutive days (IV), 2) administration of 8.3 mg/kg bwt of amikacin sulphate into one TCJ by direct IA injection once daily for three consecutive days (IA), and 3) administration of 16.7 mg/kg bwt of amikacin sulphate IV and 8.3 mg/kg bwt of amikacin sulphate into one TCJ by IA injection once daily for three consecutive days (IV+IA). There was a four-day washout period between treatments, allowing approximately 18 elimination half-lives of amikacin to elapse.[1] There were three different protocol sequences with two foals completing each (IV, IA, IV+IA; IA, IV+IA, IV; IV+IA, IV, IA).For IV catheter placement and intra-articular injection, rope squeeze-induced somnolence as previously described was used to assist the foal to lie down and as a method of restraint.[2] Immediately prior to the first treatment dose of each protocol, an 8 French, double lumen, 20 cm IV catheter^c was aseptically placed in one jugular vein to facilitate administration of amikacin and venous blood sample collection. For protocols IV and IV+IA, amikacin was administered through the distally opening port on the catheter while the proximal port was used for blood sampling. A three-syringe technique was utilized via 3-way stopcock with 4-5 mL of blood drawn before a 4-5mL blood sample was collected and then the first drawn blood was returned to the foal. The collection port of the catheter was flushed with 3 mL of 1 IU/mL heparinised saline after each sampling and the administration port was flushed with 3 mL of 10 IU/mL heparinised saline every 12 hours. For synovial fluid sampling (all protocols) and amikacin administration (protocols IV+IA and IA) direct arthrocentesis into one TCJ via a dorsomedial approach with a 20-gauge needle was used. The site was aseptically prepared and blocked with 0.5 mL mepivacaine subcutaneously.For plasma amikacin concentration assays, blood collections were performed before the first amikacin dose (1T0h) and at 15 minutes, 30 minutes, and 1, 2, 4, 6, 8, 12, 16, and 24 hours following administration of dose 1 (1T0.25h, 1T0.5h, 1T1h, 1T2h, 1T4h, 1T6h, 1T8h, 1T12h, 1T16h, 1T24h), dose 2 (2T0.25h, 2T0.5h, 2T1h, 2T2h, 2T4h, 2T6h, 2T8h, 2T12h, 2T16h, 2T24h), and dose 3 (3T0.25h, 3T0.5h, 3T1h, 3T2h, 3T4h, 3T6h, 3T8h, 3T12h, 3T16h, 3T24h). Blood was also collected via direct venepuncture at 120 hours following the third amikacin dose of the last protocol (3T120h). Synovial fluid was collected at 1T0h,1T1h, 1T24h, 2T1h, 2T24h, 3T1h, and 3T24h. For protocols IV+IA and IA, the same TCJ was used for both synovial fluid collection and amikacin administration for all time points within one protocol. Right and left TCJs were alternated between the 3 protocols. Blood was placed in EDTA tubes and plasma extracted after centrifugation. Plasma and synovial fluid samples were frozen at -80ºC until analysis for amikacin concentration.Amikacin concentrations were measured using an enzyme immunoassay^d by the clinical pharmacology lab at Auburn University as previously described.[3; 4] Serial dilutions of the synovial fluid samples were performed until the samples were within the measurable range. The lowest measurable concentration of amikacin in plasma was 2.5 µg/mL and 8.0 μg/mL in synovial fluid. FOOTNOTES:a) IDEXX Foal SNAP® IgG Test., Westbrook, Maineb) AMIGLYDE-V®, Zoetis Services, LLC., Parsippany, New Jerseyc) Arrow International Inc. Teleflex, Reading, Pennsylvaniad) Emit, Syra, Siemens Healthcare Diagnostic Inc, Newark, Delaware DECLARATION OF ETHICS: The authors have adhered to the Principles of Veterinary Medical Ethics of the AVMA. REFERENCES[1] Magdesian, K.G., Wilson, W.D. and Mihalyi, J. (2004) Pharmacokinetics of a high dose of amikacin administered at extended intervals to neonatal foals. Am J Vet Res 65, 473-479. [2] Toth, B., Aleman, M., Brosnan, R.J., Dickinson, P.J., Conley, A.J., Stanley, S.D., Nogradi, N., Williams, C.D. and Madigan, J.E. (2012) Evaluation of squeeze-induced somnolence in neonatal foals. Am J Vet Res 73, 1881-1889. [3] Moser, D.K., Schoonover, M.J., Holbrook, T.C. and Payton, M.E. (2016) Effect of Regional Intravenous Limb Perfusate Volume on Synovial Fluid Concentration of Amikacin and Local Venous Blood Pressure in the Horse. Vet Surg 45, 851-858. [4] Schoonover, M.J., Moser, D.K., Young, J.M., Payton, M.E. and Holbrook, T.C. (2017) Effects of tourniquet number and exsanguination on amikacin concentrations in the radiocarpal and distal interphalangeal joints after low volume intravenous regional limb perfusion in horses. Vet Surg 46, 675-682.